Fox Chase Cancer Center Researchers: Selenium Will Have Critical Role in Prostate Cancer Treatment
ANAHEIM, CALIF. (April 20, 2005) -- Researchers at Fox Chase Cancer Center in Philadelphia have come a step closer to understanding selenium's molecular role in causing prostate cancer cells to self-destruct. According to data presented today at the 96th Annual Meeting of the American Association for Cancer Research in Anaheim, Calif., selenium helps malignant cells overcome their resistance to TRAIL-induced apopstosis (self-inflicted cell death).
Previous studies had shown that TRAIL, a cytotoxic agent being investigated as a new therapeutic agent for cancer, causes malignant cells to self-destruct. Yet some cells resist the treatment.
"Therefore, agents that sensitize malignant cells to TRAIL-mediated cell death might be of particular importance for the development of novel anti-tumor therapeutic regimens," said lead researcher Vladimir M. Kolenko MD, PhD.
Selenium, a non-metallic trace element essential to human health, could be just that agent.
"Selenium and vitamin E are the most promising dietary supplements considered for use in the reduction of prostate cancer risk," Kolenko said. "This enthusiasm is reflected in the initiation of the large National Cancer Institute sponsored trial - SELECT (Selenium and Vitamin E Chemoprevention Trial). The epidemiologic studies within SELECT will be based on 32,000 men."
With this in mind, Kolenko and colleagues went a step further and studied the effect of methylseleninic acid (MSA), a novel selenium metabolite, in inducing apoptosis in different types of prostate cancer cells (androgen-dependent LNCaP and androgen-independent, PC-3 and DU-145).
"The cytotoxic effect of TRAIL in combination with MSA in LNCaP and DU-145 cells was evaluated using a DNA fragmentation assay," Kolenko explained. "Treatment of prostate cancer cells with TRAIL alone for 24 hours induced negligible levels of apoptosis. Treatment with MSA alone also failed to induce a significant level of cell death in LNCaP cells, although it induced notable apoptosis in DU-145. However, concomitant treatment with TRAIL and MSA resulted in profound DNA fragmentation in both LNCaP and DU-145 cells" (74.3% and 61.5% correspondingly).
"Taken together our data reveal a potential mechanism for the synergistic effect of TRAIL and MSA on the induction of apoptosis in prostate cancer cells," Kolenko concluded. "The combination of TRAIL and MSA may be a novel strategy for the development of innovative therapeutic modalities targeting apoptosis-resistant forms of prostate cancer."
In addition to Kolenko, Fox Chase study authors include visiting scientist Kenya Yamaguchi, MD, PhD, urologic surgical oncologist Robert G. Uzzo, MD, summer assistant Julia Pimkina and postdoctoral associates Peter Makhov, PhD, and Konstantin Golovin, PhD.
96th Annual Meeting of the American Association for Cancer Research
Poster Session: Apoptosis 5: Death Receptors II
Exhibit Hall B-D, Anaheim Convention Center
Abstract #5349, Board #5:
Methylseleninic acid sensitizes prostate cancer cells to TRAIL-mediated apoptosis
To be presented Wednesday, April 20, 2005, from 8 a.m. to 12 noon PT
Fox Chase Cancer Center, part of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence four consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. For more information, call 1-888-FOX CHASE or (1-888-369-2427).
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